Stem-cell hemotoxicity testing firm HemoGenix this week announced the launch of a 384-well plate version of its flagship HALO bioluminescent assay system for determining the effects of drugs on hematopoietic stem cells.
HemoGenix, which has traditionally garnered the majority of its revenues from contract hemotoxicity testing, hopes that the new higher throughput format will spur direct sales of its assay kits to pharmaceutical companies wishing to perform such testing in house, HemoGenix CEO Ivan Rich said this week.
However, the company faces a significant market challenge due to the fact that hemotoxicity testing — at least compared with other types of drug toxicity testing — has been largely ignored in pharmaceutical drug screening.
HemoGenix was formed in 2000 by Rich, who is also a professor of medicine and microbiology and immunology at the University of South Carolina. Backed by a 1991 Small Business Innovation Research grant from the National Cancer Institute, Rich developed the company's flagship technology, HALO (Hematopoietic/Hemotoxicity Assays via Luminescence Output).
As its full name implies, HALO was originally designed to test for potential toxic effects that drug candidates could have on hematopoietic stem cells. It originally used primary human bone marrow, peripheral blood, or umbilical cord blood target cells in combination with a luminescence readout system. Since then, the company further developed the technology to test for toxicity using 14 separate hematopoietic cell populations from humans, non-human primates, dogs, rats, and mice.
"Some companies will say, 'We know there is going to be toxicity, and we're not really interested in going any further.'"
The technology is based on a decades-old test for hemotoxicity known as a colony-forming assay, in which colony-forming populations of cells are incubated in Petri dishes or 4-well plates along with test compounds, and then manually enumerated using microscopy.
Colony-forming assays do produce the desired information — whether a drug candidate stunts the differentiation of colony-forming cells into blood, muscle, skeletal, or even nerve cells. However, "it's really only the larger companies that can do this, because the assay is very intensive with respect to cost and personnel," Rich told CBA News.
Because of this — and in part because researchers have only relatively recently begun to understand the importance of potential drug toxicity to differentiating human stem cells — hemotoxicity testing has largely been ignored in the pharmaceutical industry. Often times, Rich said, companies will take a drug candidate all the way to animal testing stages, where it will fail due to hemotoxicity.
"Some companies will say, 'We know there is going to be toxicity, and we're not really interested in going any further,'" Rich said. "Whereas others will base their outsourcing on some anomalous effects they see during the pre-clinical stage, in animal testing.
"Most of the companies that come to us are of the latter type," he added. "They're already in pre-clinical studies, and then they start seeing toxicity occur, and say, 'Why is this occurring?' And we just tell them why it's occurring — it's relatively simple."
According to Davide Sciuscio, a professor of pharmacology at Bologna University, pharmaceutical companies have taken hemotoxicity into account for a long time, but within the context of specific therapeutic areas. Sciuscio this year co-authored a pair of papers with scientists from GlaxoSmithKline describing a new flow-based colony-forming assay strategy.
"In the context of drug discovery, as well as in drug development, testing for stem cell toxicity or hematotoxicity is very important for some classes of drugs; for example, antiviral and anticancer drugs," Sciuscio wrote in an email to CBA News. "Most of these molecules are highly toxic for rapidly proliferating cells, including not only cancer cells but also intestinal cells, bone marrow cells, et cetera.
"When testing new anticancer drugs, tests like the colony-forming unit-granulocyte/macrophage clonogenic assay decrease the risk of a lethal overdose in the first cohort of patients to which they are administered, a risk that could not be identified with current preclinical testing strategies," he added. "International studies have shown that this assay is more predictive than animal testing."
HemoGenix's Rich said he believes that one of the main reasons pharmaceutical companies have not employed hemotoxicity testing earlier in the drug-discovery process is the lack of a reliable assay suited to a screening environment. This is where HemoGenix hopes to find its niche.
"This was one of the reasons we were so lucky in getting an SBIR grant to develop HALO — hemotoxicity testing has largely been ignored," Rich said. "It's been right at the bottom of the list of most toxicity testing. We believe this is because there haven't been reliable and standardized assays to do it. We've tried to be at the forefront of that, to make sure that the assays we perform, and that people who use the kits, have a robust and reliable assay."
As a private company, HemoGenix does not disclose revenues, but according to Rich, the company has made headway by providing hemotoxicity testing services to "a number of small, medium, and some of the largest pharmaceutical companies." Rich said that the companies typically interested in HALO are those developing drugs for cancer, inflammatory diseases, and sometimes viruses.
In addition, he said, the bulk of HemoGenix's revenues have come from contract research, which was the main driver behind providing a platform with increased throughput.
"We've gone form a 96-well format to a 384-well format, and that really allows us to target drug-discovery screening," Rich said. "With the 96-well format it's OK, but it's not really high throughput, and it's not automated.
"It was a very easy thing for us to go from a contract service to a kit because the platform itself was developed in such a way that it is not only easy for me to use, but also for our customers," he added. "We're just trying to transfer that easiness over to them. A lot of companies don't want to outsource — they would like to do things internally."
HemoGenix's HALO kits contain all the reagents and well plates that the company uses in its internal hemotoxicity testing services. Essentially, customers using it in house need to supply their desired stem cells, as well as a bioluminescence plate reader.
Rich said that the company is also targeting basic research labs and companies working in stem cell transplantation and core blood storage, but that drug screening remains the most potentially lucrative area.
Currently, HemoGenix's biggest competitor is the well-established colony forming assay, the reagents for which are available through several companies, and which has remained essentially unchanged for decades, HemoGenix says.
"There are companies out there that sell just the reagents for hemotoxicity testing, but you have to manually enumerate using a microscope," Rich said. "But this platform has been specifically developed for drug discovery. With the 96-well format, and now the 384-well format, as well as our intellectual property, I consider us well ahead of anything else there might be."